A Phase II Randomized Trial of Recombinant Fowlpox and Recombinant Vaccinia Virus Expressing PSA in Patients With Adenocarcinoma of the Prostate


Phase 2
18 Years
N/A
Not Enrolling
Male
Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

A Phase II Randomized Trial of Recombinant Fowlpox and Recombinant Vaccinia Virus Expressing PSA in Patients With Adenocarcinoma of the Prostate


OBJECTIVES:

I. Determine the toxicity and maximum tolerated dose of recombinant fowlpox
prostate-specific antigen (PSA) vaccine in patients with advanced adenocarcinoma of the
prostate.

II. Determine whether vaccination with recombinant fowlpox-PSA vaccine is associated with
antitumor activity in these patients.

III. Determine the efficacy of prime and boost regimens using recombinant fowlpox-PSA
vaccine and recombinant vaccinia-PSA vaccine in these patients.

IV. Compare the PSA-specific T-cell response in patients treated with recombinant
fowlpox-PSA vaccine followed by recombinant vaccinia-PSA vaccine vs the same vaccines but in
reverse order.

OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of recombinant
fowlpox prostate-specific antigen (PSA) vaccine.

SAFETY COHORT: The first cohort of 3 patients receives vaccination with recombinant
fowlpox-PSA vaccine intramuscularly (IM). Treatment repeats every 4 weeks for 3 courses. In
the absence of unacceptable toxicity in the first cohort, the second cohort of 3 patients
receives the same vaccine at the dose level immediately higher than the first cohort dose
level. In the presence of unacceptable toxicity in the first cohort, the second cohort of 3
patients receives the same vaccine at a dose level lower than the first cohort dose level.
The maximum tolerated dose (MTD) is the dose preceding that at which 1 of 6 patients
experiences grade 3 or worse dose-limiting toxicity.

Subsequent patients are assigned to one of two vaccination groups based on prior treatment
with recombinant vaccinia-PSA vaccine:

GROUP A (no prior recombinant vaccinia-PSA vaccine): Patients are randomized to one of two
vaccination arms:

ARM I: Patients receive recombinant fowlpox-PSA vaccine IM at the MTD from the safety cohort
every 4 weeks for 3 courses. Patients then receive recombinant vaccinia-PSA vaccine
intradermally every 4 weeks for 2 courses.

ARM II: Patients receive the same vaccines as in arm I but in reverse order.

GROUP B (prior recombinant vaccinia-PSA vaccine): Patients receive treatment as in arm I,
group A.

GROUPS A AND B: Patients with stable or responding disease at 6 months after completion of
vaccination therapy may continue treatment on the group and arm to which they were
originally assigned. Treatment repeats every 6-9 months in the absence of disease
progression.

Patients are followed monthly for 6 months and then every 3 months thereafter.


Inclusion Criteria:



- Histologically proven adenocarcinoma of the prostate with evidence of metastatic
disease including any of the following:

- Lymph node positive and prostate-specific antigen (PSA) at least 10 ng/mL

- Bone scan positive and PSA at least 10 ng/mL

- Prior radical prostatectomy with rising PSA and PSA at least 2 ng/mL

- Prior radiotherapy and PSA at least 10 ng/mL

- Prior cryosurgery and PSA at least 10 ng/mL

- PSA criteria does not apply to patients who are assigned to group B of this
study and were previously treated on vaccine trial DFCI-96079

- No symptomatic metastatic disease (no bony pain)

- Complete HLA typing required

- Performance status - ECOG 0 or 1

- WBC greater than 2,000/mm^3

- Platelet count greater than 100,000/mm^3

- Bilirubin less than 2.0 mg/dL

- SGPT less than 4 times upper limit of normal

- Creatinine less than 4.0 mg/dL

- No altered immune function such as eczema

- No autoimmune diseases such as the following:

- Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia

- Systemic lupus erythematosus, Sjögren's syndrome, or scleroderma

- Myasthenia gravis

- Goodpasture's syndrome

- Addison's disease, Hashimoto's thyroiditis, or active Graves' disease

- HIV negative

- No allergy or untoward reaction to prior vaccinia (smallpox) vaccination

- No hypersensitivity to eggs

- No prior or concurrent extensive eczema or skin disorders (e.g., extensive psoriasis,
burns, impetigo, or disseminated zoster)

- No other concurrent serious illness

- No active infection requiring antibiotics until infection has cleared and antibiotics
have been stopped for at least 3 days

- Fertile patients must use effective contraception

- No close contact or household contact with the following high-risk individuals for at
least 2 weeks after each vaccination:

- Children under age 5

- Pregnant or nursing women

- Individuals with prior or concurrent extensive eczema or other eczematoid skin
disorders

- Individuals with other acute, chronic, or exfoliative skin conditions (e.g.,
atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other
open rashes or wounds)

- Immunodeficient or immunosuppressed individuals (by disease or therapy) such as
those with HIV infection

- See Disease Characteristics

- See Endocrine therapy

- Prior vaccinia (smallpox) immunization required

- No other concurrent biologic therapy (e.g., interferon or interleukin) for cancer

- No prior chemotherapy for metastatic disease

- No concurrent anticancer chemotherapy

- No prior hormonal therapy for metastatic disease

- Prior neoadjuvant hormonal therapy followed by prostatectomy or radiotherapy allowed

- Patients previously treated with recombinant vaccinia-PSA vaccine may have hormonal
therapy since discontinuing that treatment (Group B)

- No concurrent hormonal therapy or steroids

- See Disease Characteristics

- See Endocrine therapy

- No concurrent radiotherapy

- See Disease Characteristics

- See Endocrine therapy

- No prior splenectomy

- At least 3 days since prior antibiotics

- No concurrent immunosuppressive treatment (e.g., after organ transplantation)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PSA response

Outcome Description:

PSA response is assessed at 3 successive monthly determinations, starting 28 days after the final vaccine dose.

Outcome Time Frame:

Up to 3 months after the final vaccine dose

Safety Issue:

No

Principal Investigator

Joseph Paul Eder

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02319

NCT ID:

NCT00005039

Start Date:

January 2000

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms
  • Vaccinia

Name

Location
Dana-Farber Cancer Institute Boston, Massachusetts  02115